Early Development Scale-Up of a Structurally-Challenging 5-Lipoxygenase Activating Protein (FLAP) Inhibitor

被引：7

作者：

Mulder, Jason A. ^{[1
]}

Gao, Joe ^{[1
]}

Fandrick, Keith R. ^{[1
,3
]}

Zeng, Xingzhong ^{[1
]}

Desrosiers, Jean-Nicolas ^{[1
,4
]}

Patel, Nitinchandra D. ^{[1
]}

Li, Zhibin ^{[1
,5
]}

Rodriguez, Sonia ^{[1
]}

Lorenz, Jon C. ^{[1
]}

Wang, Jun ^{[1
]}

Ma, Shengli ^{[1
,6
]}

Fandrick, Daniel R. ^{[1
]}

Grinberg, Nelu ^{[1
,7
]}

Lee, Heewon ^{[1
]}

Bosanac, Todd ^{[2
]}

Takahashi, Hidenori ^{[2
,8
]}

Chen, Zhidong ^{[2
,9
]}

Bartolozzi, Alessandra ^{[2
]}

Nemoto, Peter ^{[2
,10
]}

Busacca, Carl A. ^{[1
]}

Song, Jinhua J. ^{[1
]}

Yee, Nathan K. ^{[1
]}

Mahoney, Paige E. ^{[2
]}

Senanayake, Chris H. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Chem Dev US, 900 Ridgebury Rd, Ridgefield, CT 06877 USA

[2] Boehringer Ingelheim Pharmaceut Inc, Med Chem US, 900 Ridgebury Rd, Ridgefield, CT 06877 USA

[3] LAM Therapeut, 530 Old Whitfield St, Guilford, CT 06437 USA

[4] Pfizer Inc, 558 Eastern Point Rd, Groton, CT 06340 USA

[5] Locke Lord LLP, Brookfield Pl,200 Vesey St,20th Floor, New York, NY 10281 USA

[6] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA

[7] 274 Aspetuck Ridge Rd, New Milford, CT 06776 USA

[8] Schrodinger, 120 West 45th St,17th Floor,Tower 45, New York, NY 10036 USA

[9] 160 Willow Springs, New Milford, CT 06776 USA

[10] Synovel, 42 Lake Ave Ext 222, Danbury, CT 06811 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2017年 / 21卷 / 09期

关键词：

PALLADIUM; DISCOVERY; POTENT; LICL; ACID;

D O I：

10.1021/acs.oprd.7b00202

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A practical and efficient synthesis of the FLAP inhibitor 1 was developed addressing multiple scale-up and safety concerns posed by the established synthesis and utilized a resolution strategy (replacing supercritical fluid chromatography (SFC) separation) for expedient access to the key structural component of 1: the challenging chiral quaternary center. Also highlighted are in situ IR monitoring, condensation to form the 1,2,4-oxadiazole ring, and an efficient Suzuki-Miyaura coupling.

引用

页码：1427 / 1434

页数：8

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